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Science: How 'mutant' molecules fight for survival

29 February 1992

By JOHN EMSLEY

Chemists in the US believe they have discovered the chemical equivalent
of biological selection. The team, led by Julius Rebek of the Massachusetts
Institute of Technology, was responsible for making the first synthetic
self-replicating molecule two years ago (New Scientist, Science, 28 April
1990). Now the same chemists have carried out experiments with two more
self-replicating molecules, and discovered that they can cooperate, catalysing
each other’s formation. Furthermore, when one of the molecules is exposed
to ultraviolet light and is ‘mutated’, it becomes ‘aggressive’ and takes
over the system. According to Rebek and his colleagues, this is evidence
that evolution can be modelled at the molecular level (Science, vol 255,
p 848)

Rebek and his colleagues studied the reaction between a complex imide
ester (E) and an adenine derivative (A). These bond together to form a molecule
of product (A-E), eliminating a phenol. The product has the ability to attract
an E molecule to its A end, and an A molecule to its E end. It does this
by forming hydrogen bonds, the same bonds which DNA uses to ‘recognise’
the components needed for its own replication.

The attracted A and E molecules react to form a new product molecule,
and the two completed molecules separate. The replication process can be
repeated indefinitely, provided there is a constant supply of A and E molecules.

Rebek and his colleagues also experimented with adenine derivatives
to which they attached slightly different side groups. They took the products
A1-E1 of one set of modified molecules and added it to a reaction vessel
containing a different set, A2 and E2. Unexpectedly, they found that the
added A1-E1 catalysed the formation of its counterpart, A2-E2. Rebek says
this cooperative self-replication is understandable because the added A1-E1
is very similar to the A2-E2 being formed, and can also attract A2 and E2
molecules to itself by hydrogen bonding.

Rebek’s team then chose an A molecule with a side group which blocked
its hydrogen bonding, causing the A-E product to form more slowly. They
also found that this reaction was catalysed by other kinds of A-E. The blocked
version of A could be changed to the unhindered version by ultraviolet light.
This produced a ‘mutant’, which quickly took advantage of its greater reactivity
to scavenge all the E and form its own A-E product at the expense of its
‘parent’.